Oxidations of C-N systems
Oxidation of C-S systems
Oxidations of aldehyde and alcohol
Aromatic hydroxylations
Reductions
Carbonyl reductions
Nitro reductions
Azo reductions
Reductive dehalogenation
Hydrolyses
Ester hydrolysis
Amide hydrolysis
Phase II transformations
Glucuronic acid conjugation
O-glucuronidation
N-glucuronidation
S-glucuronidation
C-glucuronidation
Sulfuric acid conjugation
Amino acid conjugation
Acetyl conjugation
Methyl conjugation
Glutathione conjugation
Hydration or water conjugation
3.5.1.2 Selected Examples of Metabolic Reactions
The previous section listed the various reactions that the body can inflict upon a drug
molecule. This section presents brief examples of a number of these reactions.
Oxidation: Aliphatic Carbon Atoms.Oxidation at the terminal carbon atom of an
alkyl substituent is ω-oxidation; oxidation of the carbon atom located second from the
end is ω-1 oxidation. Unless specifically catalyzed by an enzyme,ω-1 oxidation tends
to occur more frequently. The anticonvulsant drug ethosuximide is metabolized at both
theωandω-1 position.
Oxidation: Alkene Epoxidation. Alkenes may react to produce epoxides (alterna-
tively, sometimes, the alkenes do not react and are metabolically stable). The epoxide
is unstable and is subject to ring opening via a nucleophilic attack. The anticonvulsant
drug carbamazepine is metabolized via epoxidation to yield carbamazepine-10,11-
epoxide; in turn, this is rapidly opened to yield carbamazepine-10,11-diol.
Oxidation: Carbons Adjacent to sp^2 Atoms. Carbon atoms that are situated adjacent
to imine, carbonyl, or aromatic groups are frequently oxidized. This reaction appears to
be catalyzed by the cytochrome P-450 enzyme system. Typically, a hydroxyl group is
attached to the carbon as part of the oxidation process.
DESIGNING DRUG MOLECULES TO FIT RECEPTORS 147